With demographics shifting towards an older population and with more people living more active lifestyles, the number of orthopaedic injuries and disorders continues to rise. In the United States alone, there were more than 6 million fractures each year from 1992 to 1994 (Praemer et al. American Academy of Orthopaedic Surgeons 1999 182). In 1995, there were 216,000 total knee replacements, 134,000 total hip replacements, and close to 100,000 bone grafting procedures performed. Traditionally, autografts and allografts have been used by orthopaedic surgeons to repair fractures and other bone defects. However, limitations including donor-site morbidity, risk of disease transfer, potential immunogenicity, and insufficient supply has led investigators to search for alternative bone repair materials.
Since the main mineral component of bone is a complex calcium phosphate system called apatite, hydroxyapatite and other materials within the calcium phosphate family have been and continue to be extensively investigated (DeMaeyer et al. J. Biomed. Mater. Res. 2000 52:95-106; Keller, L. and Dollase, W. A. J. Biomed. Mater. Res. 2000 49:244-249; Zeng et al. Biomaterials 1999 20:443-451; Ma et al. J. Biomed. Mater. Res. 2001 54:284-293; and Duracan, C. and Brown, P. W. J. Biomed. Mater. Res. 2000 51:726-734). Further, calcium phosphate ceramics have been reported to be osteoconductive and to directly bond to bone (Jarcho, M. Clin. Orthop. Rel. Res. 1981 157:259-278; Kitsugi et al. Clin. Orthop. Rel. Res. 1988 234:280-290). In addition, calcium phosphate ceramics are believed to serve as precursors to bone apatite formation in vivo. Accordingly, the good bone compatibility of calcium phosphate ceramics is indicative of their suitability for repair or replacement of damaged or diseased bone. However, the brittleness of these materials limits their widespread use in orthopaedics, particularly in load-bearing applications.
Accordingly, various attempts have been made to overcome this limitation. One example has been to prepare composites of these ceramics with bioresorbable polymeric materials such as collagen and polymers of lactic acid and glycolic acid (TenHuisen et al. J. Biomed. Mater. Res. 1995 29:803-810; Yasunaga et al. J. Biomed. Mater. Res. 1999 47:412-419; Zhang et al. J. Biomed. Mater. Res. 1999 45:285-293; Devin et al. J. Biomater. Sci. Polymer. Edn. 1996 7:661-669; Boeree et al. Biomaterials 1993 14:793-796). In general, these composites are made porous in order to create a 3-dimensional scaffold that allows the ingrowth of new bone and the eventual replacement of the scaffold with new skeletal tissue (Zhang et al. J. Biomed. Mater. Res. 1999 45:285-293; Devin et al. J. Biomater. Sci. Polymer. Edn. 1996 7:661-669). In these composites, the ceramic typically comprises a calcium phosphate compound with moderate to high crystallinity (TenHuisen et al. J. Biomed. Mater. Res. 1995 29:803-810; Yasunaga et al. J. Biomed. Mater. Res. 1999 47:412-419; Zhang et al. J. Biomed. Mater. Res. 1999 45:285-293; Devin et al. J. Biomater. Sci. Polymer. Edn. 1996 7:661-669; Boeree et al. Biomaterials 1993 14:793-796).
In contrast, bone apatite is poorly crystalline and non-stoichiometric due to the presence of other ions such as magnesium and carbonate ions (Posner, A. S. and Betts, F. Acc. Chem. Res. 1975 8:273-281; Bigi et al. Calcif. Tissue Int. 1992 50:439-444). Further, crystalline forms of hydroxyapatite have been shown to resorb at a slower rate than that of new bone formation. In fact, the rate of new bone formation coincides more closely with the resorption rate of poorly crystalline or amorphous calcium phosphate ceramics (Frayssinet et al. Biomaterials 1993 14:423-429; Klein et al. J. Biomed. Mater. Res. 1983 17:769-784; Knaack et al. J. Biomed. Mater. Res. (Appl. Biomater.) 1998 43:399-409).
In the present invention, crystalline hydroxyapatite is replaced with a poorly crystalline or amorphous calcium phosphate ceramic believed to resorb concurrently with new bone growth. Also, the degradation of the amorphous calcium phosphate forms alkali products that serve to buffer the acidic degradation product of either lactic or glycolic acid in a composite of the two materials.